Breakthrough in treatment for world’s leading cause of kidney failure in children
20 October 2023
A potential treatment for the world’s leading cause of kidney failure in children needing dialysis has been discovered by an international team of scientists. The University of Bristol-led breakthrough is published today [19 October] in Med.
The commonest cause of kidney failure in children is due to toxin producing bacteria that enters the circulation through the gut resulting in a disease called Haemolytic Uraemic Syndrome (HUS). There are different types of HUS – the most common is called Shiga toxin-associated haemolytic uraemic syndrome (STEC-HUS). As one of the most common causes of kidney problems in people of all ages, it can be particularly devastating in young children, often requiring kidney dialysis, with around one in 20 children developing life-long kidney failure or dying.
STEC-HUS commonly happens after a gut infection, associated with bloody diarrhoea. Exactly why the kidney is so susceptible to injury in STEC-HUS has until now, remained unclear. The research, funded by the Medical Research Council and Kidney Research UK and led by scientists from Bristol Renal, wanted to identify the mechanism underpinning the disease pathway.
Using laboratory models, the team found a specific cell in the kidney called the podocyte — which plays a crucial role in renal function — is targeted by the Shiga toxin and then ‘talks’ to local blood vessels causing small blood clots to form. This is due to the activation of the ‘complement’ pathway, and can lead to an eventual loss of kidney function.
Critically, the team demonstrated in both mouse models and in human kidney cells that STEC-HUS can be successfully treated by inhibiting the complement pathway early in the disease process with a drug called Eculizumab.
Richard Coward, Professor of Renal Medicine at the University of Bristol and Consultant Paediatric Nephrologist at Bristol Royal hospital for Sick Children, and one of the study's lead authors said: "As a children's kidney doctor one of the most difficult and devastating diseases we treat is STEC-HUS, which causes kidney failure and death in some children. This is normally caused by a bacteria that enters the circulation via the gut causing bloody diarrhoea.
"We have now discovered that a cell in the kidney called the podocyte is a key target cell of Shiga toxin and that it can be treated if the ‘complement’ pathway is blocked in the blood early in the disease."
Dr Aisling McMahon, Executive director of research and policy at Kidney Research UK added: "This research has not only shown exactly how Shiga toxin is able to target the kidney and cause such devastating damage but has also discovered a way in which HUS could be stopped in its tracks using a drug that is already in clinical use. This is another great example of the importance of research in identifying new treatment options for patients, and we look forward to the next steps in this project."
The research team has demonstrated that early use of Eculizumab can prevent Shiga-toxin driven kidney failure and the drug has therapeutic potential for this devastating disease that can result in life-long dialysis, and death, for some children.
The next steps for the researchers will be to understand how quickly Eculizumab needs to be given and carry out more early trials in children with STEC-HUS.
The international team included researchers from Bristol Renal at the University of Bristol; Bristol Royal Hospital for Sick Children, UK; Hospital for Sick Children in Toronto, Canada; Mary Lyon Centre at MRC Harwell, Oxfordshire, UK; University of Manchester, UK; School of Medicine at Cardiff University, UK and Arkana Laboratories in Arizona, USA.
'Shiga toxin targets the podocyte causing Haemolytic Uraemic Syndrome through endothelial complement activation' by Bowen et al. in Med [open access]
About Kidney Research UK
Kidney Research UK is the leading charity in the UK focused on funding research into the prevention, treatment, and management of kidney disease. Our vision is the day when everyone lives free from kidney disease and for more than 60 years the research we fund has been making an impact. But kidney disease is increasing as are the factors contributing to it, such as diabetes, cardiovascular disease, and obesity, making our work more essential than ever.
At Kidney Research UK we work with clinicians and scientists across the UK, funding and facilitating research into all areas of kidney disease. We collaborate with partners across the public, private and third sectors to prevent kidney disease and drive innovation to transform treatments.
Over the last ten years we have invested more than £58 million into research. We lobby governments and decision makers to change policy and practice to ensure that more than 3 million people living with kidney disease in the UK have access to the most effective care and treatment, and to make kidney disease a priority.
Most importantly, we also work closely with patients, ensuring their voice is heard and is at the centre of everything we do, from deciding which research to invest in to how we plan our priorities and our work across the charity.
About the Medical Research Council
The Medical Research Councilis at the forefront of scientific discovery to improve human health. Founded in 1913 to tackle tuberculosis, the MRC now invests taxpayers’ money in some of the best medical research in the world across every area of health. Thirty-three MRC-funded researchers have won Nobel prizes in a wide range of disciplines, and MRC scientists have been behind such diverse discoveries as vitamins, the structure of DNA and the link between smoking and cancer, as well as achievements such as pioneering the use of randomised controlled trials, the invention of MRI scanning, and the development of a group of antibodies used in the making of some of the most successful drugs ever developed. Today, MRC-funded scientists tackle some of the greatest health problems facing humanity in the 21st century, from the rising tide of chronic diseases associated with ageing to the threats posed by rapidly mutating micro-organisms.